Pathological Findings in Fetuses Terminated for Suspected Lower Urinary Tract Obstruction: Experience From a High-Risk Fetal Center in Canada.

PURPOSE: Pregnancies complicated by prenatally suspected lower urinary tract obstruction (LUTO) can be associated with high rates of terminations due to potentially poor outcomes. Herein, we assessed autopsy findings of fetuses terminated for suspected LUTO to evaluate the prenatal diagnostic accuracy and spectrum of underlying pathologies. MATERIALS AND METHODS: We performed a retrospective review of all pregnancies referred to a high-risk fetal center in a universal access to care health care system for suspected LUTO that opted for termination of pregnancy between 2009 and 2022. Ultrasound features, genetic investigations, placental findings, and distribution of postmortem diagnoses were assessed. RESULTS: Of a total of 190 pregnancies with suspected LUTO evaluated during the study period, 79 (42%) were terminated. We excluded 35 fetuses with incomplete data, resulting in 44 available for analysis. Pregnancies were terminated at a mean gestation of 22 ± 5 weeks. A LUTO diagnosis was confirmed in 37 (84.1%) fetuses (35 males, 2 females), and the remaining 7 showed other pathologies. Pulmonary hypoplasia was found in 62.2% (n = 23) and placental pathologies in 56.8% of confirmed LUTO compared to 33.4% and 71.4% in non-LUTO cases, respectively. Overall, a total of 31 fetuses underwent additional prenatal investigations with genetic anomalies detected only in fetuses with a confirmed LUTO diagnosis (13.6%). CONCLUSIONS: In our health care system, almost half of prenatally suspected LUTO pregnancies are terminated. The sonographic diagnostic accuracy for LUTO is reasonable at 84%. However, the remaining 16% still had significant pathologies. Genetic abnormalities are uncommon and rarely the trigger for pregnancy terminations.

Deep-learning computer vision can identify increased nuchal translucency in the first trimester of pregnancy.

OBJECTIVE: Many fetal anomalies can already be diagnosed by ultrasound in the first trimester of pregnancy. Unfortunately, in clinical practice, detection rates for anomalies in early pregnancy remain low. Our aim was to use an automated image segmentation algorithm to detect one of the most common fetal anomalies: a thickened nuchal translucency (NT), which is a marker for genetic and structural anomalies. METHODS: Standardized mid-sagittal ultrasound images of the fetal head and chest were collected for 560 fetuses between 11 and 13 weeks and 6 days of gestation, 88 (15.7%) of whom had an NT thicker than 3.5 mm. Image quality was graded as high or low by two fetal medicine experts. Images were divided into a training-set (n = 451, 55 thick NT) and a test-set (n = 109, 33 thick NT). We then trained a U-Net convolutional neural network to segment the fetus and the NT region and computed the NT:fetus ratio of these regions. The ability of this ratio to separate thick (anomalous) NT regions from healthy, typical NT regions was first evaluated in ground-truth segmentation to validate the metric and then with predicted segmentation to validate our algorithm, both using the area under the receiver operator curve (AUROC). RESULTS: The ground-truth NT:fetus ratio detected thick NTs with 0.97 AUROC in both the training and test sets. The fetus and NT regions were detected with a Dice score of 0.94 in the test set. The NT:fetus ratio based on model segmentation detected thick NTs with an AUROC of 0.96 relative to clinician labels. At a 91% specificity, 94% of thick NT cases were detected (sensitivity) in the test set. The detection rate was statistically higher (p = 0.003) in high versus low-quality images (AUROC 0.98 vs. 0.90, respectively). CONCLUSION: Our model provides an explainable deep-learning method for detecting increased NT. This technique can be used to screen for other fetal anomalies in the first trimester of pregnancy.

The Toronto nomogram: A Bayesian meta-regression derived prenatal ultrasound index to predict lower urinary tract obstruction and prune belly syndrome.

INTRODUCTION: A nomogram for predicting the diagnosis of lower urinary tract obstruction (LUTO) based on an antenatal ultrasound index generated from a Bayesian Meta-regression analysis has been in development and noted with superior diagnostic accuracy compared to the keyhole sign (KHS). We aim to assess the accuracy of the nomogram in expanded diagnostic utilization to predict LUTO. METHODOLOGY: The validation of the nomogram for expanded diagnostic utilization was based on data from a prospective institutional antenatal clinic database between January 2020 and June 2022. Diagnostic accuracy indices were determined for confirmed postnatal diagnosis of LUTO or prune belly syndrome (PBS). Receiver operating characteristics (ROC) curves were generated to compare the area under the curve (AUC) of the nomogram versus KHS. RESULTS: Based on 84 male fetuses with antenatal ultrasound of moderate-severe hydronephrosis (PUV n = 15, PBS n = 4), the KHS had 26.3% (95%CI 9.1-51.2) sensitivity and 100% (95%CI 94.4%-100%) specificity, with 14 false-negatives. The nomogram showed a 84.2 (95%CI 60.4%-96.6%) sensitivity and 95.4 (95%CI 87.1%-99%) specificity with three false-positives. The nomogram also had a superior AUC compared to KHS (0.98 vs. 0.63). CONCLUSION: The nomogram can be used as a valuable tool to trigger further postnatal screening and provide individualized risk assessments to families during prenatal counseling.

Associations and outcomes of prenatally detected rhombencephalosynapsis.

OBJECTIVE: To describe the association between prenatal imaging and neurodevelopmental outcomes of fetuses with rhombencephalosynapsis (RES). STUDY DESIGN: Thirty-four pregnancies complicated by RES were identified from our institutional databases based on US and/or MRI findings. Genetic testing results were gathered. In cases of termination of pregnancy, we studied the association between prenatal imaging and neuropathologic findings. For those who opted for expectant management, comprehensive developmental assessments and postnatal MRI imaging were evaluated. RESULTS: Over one third of fetuses in our cohort had complete RES. Common intracranial anomalies identified were mesencephalosynapsis, aqueduct stenosis and diencephalosynapsis. The degree of RES was not associated with the frequency of additional central nervous system anomalies. MRI had a good correlation with neuropathologic findings with regard to the degree of RES, aqueduct stenosis and mesencephalosynapsis. Postmortem autopsy showed that one third of our cases had VACTERL-H and almost all of those had complete RES. All liveborn neonates(n = 6) had aqueduct stenosis requiring ventriculoperitoneal shunting within days of delivery (median 5 days). While a large proportion of prenatally suspected complete RES were found to have partial RES on postnatal imaging, prenatal diagnosis of aqueduct stenosis remained unchanged. All children that were at least 2 years old (n = 3) had global developmental delay. CONCLUSION: Prenatal assessment of the RES severity is challenging and may be unreliable. Nevertheless, postnatal prognosis is poor for both complete and partial RES. Associated aqueductal stenosis, can be reliably assessed prenatally and this may contribute to worse postnatal prognosis than the degree of RES.

Maternal "mirror" syndrome: Evaluating the benefits of fetal therapy.

OBJECTIVE: To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome. STUDY DESIGN: A multicenter retrospective study of all cases of fetal hydrops complicated by maternal "mirror" syndrome and treated by any form of fetal therapy between 1995 and 2022. Medical records and ultrasound images of all cases were reviewed. "Mirror" syndrome was defined as fetal hydrops and/or placentomegaly associated with the maternal development of pronounced edema, with or without pre-eclampsia. Fetal hydrops was defined as the presence of abnormal fluid collections in ≥2 body cavities. RESULTS: Twenty-one pregnancies met the inclusion criteria. Causes of fetal hydrops and/or placentomegaly included fetal lung lesions (n = 9), twin-twin transfusion syndrome (n = 6), severe fetal anemia (n = 4), and others (n = 2). Mean gestational age at "mirror" presentation was 27.0 ± 3.8 weeks. Maternal "mirror" syndrome was identified following fetal therapeutic intervention in 14 cases (66.6%). "Mirror" symptoms resolved or significantly improved before delivery in 8 (38.1%) cases with a mean interval from fetal intervention to maternal recovery of 13.1 days (range 4-35). Three women needed to be delivered because of worsening "mirror" syndrome. Of the 21 pregnancies treated (27 fetuses), there were 15 (55.5%) livebirths, 7 (25.9%) neonatal deaths and 5 (18.5%) intra-uterine deaths. CONCLUSION: Following successful treatment and resolution of fetal hydrops, maternal "mirror" syndrome can improve or sometimes completely resolve before delivery. Furthermore, the recognition that "mirror" syndrome may arise only after fetal intervention necessitates hightened patient maternal surveillance in cases of fetal hydrops.

Revisiting the Implications of a Wide or Narrow Fetal Cavum Septi Pellucidi.

OBJECTIVES: To investigate short-term neonatal developmental outcomes in fetuses with an isolated wide or narrow cavum septi pellucidi (CSP) using new reference ranges. METHODS: A cross-sectional study on fetuses at 16 + 0 to 36 + 6 weeks of gestation between December 2020 and January 2022. CSP width reference ranges were constructed from low-risk pregnancies. Wide and narrow CSPs were defined as measurements above the 95th percentile and below the 5th percentile, respectively. For the primary outcome fetuses with normal neurosonograms were included. Neonatal developmental outcomes were assessed using the Survey of Well-being of Young Children (SWYC). RESULTS: A total of 352 fetuses were included in this study, of whom 138 were healthy and had uncomplicated neonatal outcomes. These fetuses constituted the control group and were used to construct the CSP width reference ranges. Of 185 fetuses in the neurosonography group, 9.7% had wide and 7.6% had narrow CSPs, of whom 33.3% and 22.2%, respectively, scored below the SWYC threshold for expected developmental milestones, a rate similar to that reported in the general population. CONCLUSIONS: The presence of a prenatally isolated wide or narrow CSP does not appear to increase the risk of neonatal neurodevelopmental delay.

Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes.

BACKGROUND: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. METHODS: From 2016-2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). RESULTS: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. CONCLUSION: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Agenesis of the corpus callosum: What to tell expecting parents?

Agenesis of the corpus callosum (ACC) is one of the most common brain malformations, with an incidence estimated to range from 0.5 to 70 in 10,000 among the general population. Prenatal diagnosis is made via ultrasound; however, fetal MRI is useful to confirm or exclude the presence of associated cerebral abnormalities-mostly cortical malformations-that may affect postnatal prognosis. When no additional central nervous system (CNS) or extra CNS anomalies are identified and no genetic cause is found, an isolated ACC is diagnosed. Overall, in cases of ACC, an underlying genetic cause can be identified in up to 12.5% with chromosomal microarray (CMA) and up to 47% with whole exome sequencing (WES). In cases where ACC is the only anomaly detected, the yield of WES is 30%. Postnatal outcomes are variable and depend on whether the condition is isolated or not. In truly isolated ACC, outcomes range from normal in 65% of cases through mild to severe neurodevelopmental impairments in 35% of cases. An interdisciplinary team of medical experts is key in guiding parents toward informed decision-making in pregnancies complicated by ACC. Considering current and expected advancements in genetic testing and imaging technologies in upcoming years, we herein summarize current recommendations for the management and prenatal counseling of expecting parents of fetuses with ACC. Our review pertains primarily to expecting parents of fetuses with complete ACC.

Fetal macrocephaly: Pathophysiology, prenatal diagnosis and management.

Macrocephaly means a large head and is defined as a head circumference (HC) above the 98th percentile or greater than +2SD above the mean for gestational age. Macrocephaly can be primary and due to increased brain tissue (megalocephaly), which in most cases is familial and benign or secondary. The latter may be due to various causes, including but not limited to communicating or non-communicating hydrocephalus, cerebral edema, focal and pericerebral increased fluid collections, thickened calvarium and brain tumors. Megalocephaly can be syndromic or non-syndromic. In the former, gyral and structural CNS anomalies are common. It is important to exercise caution when considering a diagnosis of megalocephaly due to limitations in the accuracy of HC measurement, lack of nomograms for specific populations, inconsistencies between prenatal and postnatal HC growth curves and progression over time. The degree of macrocephaly is important, with mild macrocephaly ≤2.5SD carrying a good prognosis, especially when one of the parents has macrocephaly and normal development. Cases in which the patient history and/or physical exam are positive or when parental HC are normal are more worrisome and warrant a neurosonogram, fetal MRI and genetic testing to better delineate the underlying etiology and provide appropriate counseling.

Performance of comprehensive first trimester fetal anatomy assessment.

OBJECTIVE: Ultrasound assessment of the fetal anatomy and fetal echocardiography are feasible in the first trimester of pregnancy. This study was designed to assess the performance of a comprehensive fetal anatomy assessment in a high-risk population at a tertiary fetal medicine unit. METHODS: A retrospective review of high-risk patients undergoing comprehensive fetal anatomy ultrasound assessment between 11 weeks and 13 + 6 weeks of gestation was conducted. Findings of the early anatomy ultrasound scan were compared with those of the second trimester anatomy scan, and birth outcomes or post-mortem results. RESULTS: Early anatomy ultrasounds were performed in 765 patients. The sensitivity of the scan for detecting fetal anomalies compared to the birth outcome was 80.5% (95% CI 73.5-86.3) and specificity was 93.1% (95%CI 90.6-95.2). Positive and negative predictive values were 78.5% (95% CI 71.4-84.6) and 93.9% (95% CI 91.4-95.8), respectively. The most missed and overdiagnosed abnormalities were ventricular septal defects. The second trimester ultrasound had sensitivity of 69.0% (95% CI 55.5-80.5) and specificity of 87.5% (95% CI 84.3-90.2). CONCLUSIONS: In a high-risk population, early assessments had similar performance metrics as the second trimester anatomy ultrasound. We advocate for a comprehensive fetal assessment in the care of high-risk pregnancies.

Simple prenatal imaging predictors for postnatal cerebrospinal fluid diversion surgery in fetuses undergoing in utero surgery for spina bifida.

OBJECTIVES: To determine simple prenatal imaging parameters that can easily be acquired to predict the need for postnatal CSF diversion (PCD) surgery in fetuses undergoing open fetal surgery for open spina bifida (OSB). METHODS: All fetuses with OSB that underwent open fetal surgery between June 2017 and June 2021 with available follow-up outcomes were included. Imaging parameters including clivus-supraocciput angle (CSA) on magnetic resonance imaging, transcerebellar diameter (TCD) and lateral ventricle size (Vp) on ultrasound (US), were collected pre- and postoperatively. The requirement for PCD surgery was determined at 1 year of age. The predictive strength of each parameter was determined by Receiver Operating Characteristic curve analysis. RESULTS: Among 36 babies eligible for the analyses, 41.7% required PCD by one year of age. Pre-operative Vp (AUC 0.71; 95% confidence interval [CI] 0.54-0.88; p = 0.03), TCD (AUC 0.72; 95% CI 0.55-0.89; p = 0.02) and CSA (AUC 0.72; 95% CI 0.51-0.93; p = 0.04) were fair predictors for PCD surgery. After fetal surgery, TCD (AUC 0.93; 95% CI 0.83-1.00; p < 0.0001) and CSA (AUC 0.94; 95% CI 0.83-1.00; p = 0.0005) were outstanding predictors of PCD, whereas post-operative Vp was a fair predictor (AUC 0.71, 95% CI 0.54-0.88, p = 0.03). CONCLUSION: Post-operative CSA and TCD were outstanding predictors for the need for PCD surgery.

Outcomes and management of pregnancy and puerperal group A streptococcal infections: A systematic review.

INTRODUCTION: Group A streptococcus (Streptococcus pyogenes) is one of the most lethal bacterial pathogens of humans, with increased risk of progression to septic shock and multiorgan failure in the pregnant population. The objective of this study is to systematically review the outcomes and management strategies for pregnancy and puerperal group A streptococcus infections in an effort to provide further guidance for prevention and treatment of a rare but lethal infection worldwide. MATERIAL AND METHODS: A comprehensive search using puerperium and streptococcus pyogenes terms was completed across several registered databases. A total of 902 articles investigating pregnancy and puerperal group A streptococcus infection were identified, with 40 studies fulfilling inclusion criteria of original research articles in humans published from 1990 onwards reporting four or more unique cases of group A streptococcus in pregnancy or postpartum. This study was registered in PROSPERO: CRD42020198983. RESULTS: A total of 1160 patients with pregnancy and puerperal group A streptococcus infection were identified. Most infections occurred postpartum (91.9%), with 4.7% reported antepartum and 0.6% intrapartum. Bacteremia was present in 49.0% of patients and endometritis in 45.9%. Puerperal sepsis was described in 28.2% of cases and progressed to streptococcal toxic shock syndrome in one-third of such cases. Overall, the case fatality ratio was 2.0%, with one-third of the deaths from antenatal cases including 3/22 (13.6%) cases of septic abortion and 10/46 (21.7%) antenatal cases of group A streptococcus infection. CONCLUSIONS: Group A streptococcus infection remains an important contributor to pregnancy and puerperal morbidity and mortality. Early recognition, diagnosis and aggressive management are important for favorable outcomes given the serious risk of sepsis and streptococcal toxic shock syndrome.

Timing of cesarean delivery in women with ≥2 previous cesarean deliveries.

BACKGROUND: The rate of cesarean delivery is continuously increasing with the leading indication being a previous cesarean delivery. For women with 1 previous cesarean delivery, it is generally agreed that the optimal timing of delivery by elective cesarean delivery is during the 39th week of gestation, whereas for women with ≥2 previous cesarean deliveries, the optimal delivery time remains debatable. OBJECTIVE: To assess the maternal and neonatal risks associated with elective delivery at different gestational ages ranging from 37 0/7 to 39 6/7 weeks' gestation and to compare it with expectant management among women with at least 2 previous cesarean deliveries. STUDY DESIGN: This was a retrospective, population-based cohort study of all women with at least 2 previous cesarean deliveries who delivered after 36 6/7 weeks of gestation in Ontario, Canada, between April 2012 and March 2019. Women with multifetal pregnancies or major fetal anomalies were excluded. For each completed gestational week, outcomes of women who had an elective repeat cesarean delivery at that week solely because of 2 previous cesarean deliveries were compared with the outcomes of those who were managed expectantly and delivered at a later gestational age. The primary outcome was a composite of maternal outcomes including mortality and severe maternal morbidity. Secondary outcomes were adverse neonatal outcomes. RESULTS: A total of 26,522 women met the inclusion criteria. The maternal risk was similar for elective delivery at 37 0/7 to 38 6/7 weeks of gestation compared with expectant management. However, elective delivery at 39 0/7 to 39 6/7 weeks' gestation was associated with a decreased risk for adverse outcomes when compared with expectant management (adjusted risk ratio, 0.51; 95% confidence interval, 0.29-0.91). For the neonate, elective delivery during the 37th week of gestation significantly increased the incidence of the composite adverse outcome than in an ongoing pregnancy (adjusted risk ratio, 1.68; 95% confidence interval, 1.39-2.01), but was comparable for elective delivery at 38 0/7 to 39 6/7 weeks' gestation and expectant management. The risk for an unplanned cesarean delivery increased from 6.5% before 38 weeks' gestation to 21.7% before 39 weeks' gestation and to 32.6% before 40 weeks' gestation. CONCLUSION: For women with ≥2 cesarean deliveries, elective delivery at 38 0/7 to 38 6/7 weeks' gestation likely represents the optimal balance between neonatal and maternal risk while decreasing the likelihood of an unplanned cesarean delivery.

Perinatal outcomes in women living with HIV-1 and receiving antiretroviral therapy-a systematic review and meta-analysis.

INTRODUCTION: Antiretroviral therapy-naïve pregnant women living with HIV are at an increased risk for adverse pregnancy outcomes. It remains controversial whether this risk persists with antiretroviral therapy. We conducted a systematic review and meta-analysis to evaluate whether pregnant women living with HIV and receiving antiretroviral therapy antenatally, are at an increased risk of adverse outcomes compared with HIV-negative controls. MATERIAL AND METHODS: We searched MEDLINE, Embase, International Pharmaceutical Abstracts, EBM Reviews, PubMed (non-MEDLINE records), EBSCO CINAHL Complete, Clarivate Web of Science, African Index Medicus, LILACS and Google Scholar for all observational studies comparing pregnant women living with HIV on antiretroviral therapy with HIV-negative controls from 1 January 1994 to 10 August 2021 with no language or geographic restrictions. Perinatal outcomes included preterm birth (PTB), low birthweight, small-for-gestational age and preeclampsia. Using a random-effects model we pooled raw data to generate odds ratio (OR) with 95% confidence intervals (CI) for each outcome. Sub-analyses for high and low resource countries and time of antiretroviral therapy initiation were performed. This systematic review and meta-analysis is registered with PROSPERO, number CRD42020182722. RESULTS: Of the 7900 citations identified, 27 were eligible for analysis (12 636 pregnant women living with HIV on antiretroviral therapy and 7 812 115 HIV-negative controls). ORs (95% CI) of PTB (1.88 [1.63-2.17]), small-for-gestational age (1.60 [1.18-2.17]) and low birthweight (2.15 [1.58-2.92]) were significantly higher in pregnant women living with HIV than in HIV-negative women, while the risk of preeclampsia (0.86 [0.57-1.30]) was comparable. The risk of PTB and low birthweight was higher in both high resource and low resource countries, while the risk of small-for-gestational age was higher only in the former. Preconceptional antiretroviral therapy was associated with a higher risk of PTB compared with antenatal initiation. CONCLUSIONS: Pregnant women living with HIV on antiretroviral therapy have an increased risk of PTB, low birthweight and small-for-gestational age in high resource countries, as well as PTB and low birthweight in low income countries compared with HIV-negative controls.

Doppler Ultrasound of the Fetal Descending Aorta: An Objective Tool to Assess Placental Blood Flow Resistance in Pregnancies With Discordant Umbilical Arteries.

OBJECTIVES: To determine the relationship between blood flow in the fetal descending aorta and discordant umbilical arteries (UAs). METHODS: Pulsed wave Doppler of both UAs and the descending aorta was performed at 4-weekly intervals between 14 and 40 weeks of gestation in 209 pregnant women. In datasets with discordant UAs, a linear mixed effects model was used to determine the categorical relationship between the UA pulsatility index (PI) (high, low and average) and the descending aorta PI. RESULTS: Of the 209 cases, 81 had a discordance of greater than 25% in UA PI during one of their visits. There were no differences in birth outcomes between the groups with concordant and discordant UA PIs. In the cases with discordant UA PIs, the descending aorta PI was most strongly associated with both the average UA PI (P = .008), and with the UA with the lower PI (P = .008). CONCLUSIONS: The relationship between blood flow in the descending aorta and UAs is consistent with the law for combining resistances in parallel. Measurements of the descending aorta PI, particularly in a scenario with discordant UAs, may inform the stability of the feto-placental circulation where discordant UA PIs are found.

Fetal Meconium Peritonitis - Prenatal Findings and Postnatal Outcome: A Case Series, Systematic Review, and Meta-Analysis.

PURPOSE: To describe the postnatal outcome of fetal meconium peritonitis and identify prenatal predictors of neonatal surgery. METHODS: We retrospectively reviewed all fetuses with ultrasound findings suspicious for meconium peritonitis at a single center over a 10-year period. A systematic review and meta-analysis were then performed pooling our results with previous studies assessing prenatally diagnosed meconium peritonitis and postnatal outcome. Prenatal sonographic findings were analyzed to identify predictors for postnatal surgery. RESULTS: 34 cases suggestive of meconium peritonitis were diagnosed at our center. These were pooled with cases from 14 other studies yielding a total of 244 cases. Postnatal abdominal surgery was required in two thirds of case (66.5 %). The strongest predictor of neonatal surgery was meconium pseudocyst (OR [95 % CI] 6.75 [2.53-18.01]), followed by bowel dilation (OR [95 % CI] 4.17 [1.93-9.05]) and ascites (OR [95 % CI] 2.57 [1.07-5.24]). The most common cause of intestinal perforation and meconium peritonitis, found in 52.2 % of the cases, was small bowel atresia. Cystic fibrosis was diagnosed in 9.8 % of cases. Short-term neonatal outcomes were favorable, with a post-operative mortality rate of 8.1 % and a survival rate of 100 % in neonates not requiring surgery. CONCLUSION: Meconium pseudocysts, bowel dilation, and ascites are prenatal predictors of neonatal surgery in cases of meconium peritonitis. Fetuses with these findings should be delivered in centers with pediatric surgery services. Though the prognosis is favorable, cystic fibrosis complicates postnatal outcomes.

Brain and Placental Pathology in Fetal COL4A1 Related Disease.

INTRODUCTION: Although fetal brain injury due to COL4A1 gene mutation is well documented, fetal central nervous system (CNS) and placental histopathology lack description. We report CNS and placental pathology in fetal cases with symptomatic COL4A1 mutation. METHODS: We retrieved four autopsy cases of COL4A1 related disease, confirmed by genetic sequencing after fetal brain injury was detected. RESULTS: One case was a midgestation fetus with residua of ventricular zone hemorrhage and normal placental villi. Three cases were 30-32 week gestation fetuses: two demonstrated CNS small vessel thrombosis, with CNS injury. Both demonstrated high grade placental fetal vascular malperfusion (FVM). One additionally showed villous dysmorphism, the other demonstrated mild villous immaturity. The fetus whose placenta demonstrated high grade FVM was growth restricted. A fourth fetus demonstrated schizencephaly with a CNS arteriopathy with smooth muscle cell degeneration and cerebral infarcts; the placenta demonstrated severe villous dysmorphism and low grade FVM. DISCUSSION: These cases confirm that small vessel disease is important in producing intracranial pathology in COL4A1mutation. We report an arteriopathy distinct from microvascular thrombosis and demonstrate that placental pathology is common in fetal COL4A1 related disease. This tentatively suggests that placental pathology may contribute to CNS abnormalities by affecting circulatory sufficiency.

Selective fetal reduction in complicated monochorionic twin pregnancies: A comparison of techniques.

OBJECTIVE: To compare perinatal outcomes associated with three methods of selective reduction in complicated monochorionic (MC) twin pregnancies: bipolar cord coagulation (BC), fetoscopic or ultrasound guided laser cord occlusion and radiofrequency ablation (RFA). METHODS: Retrospective cohort study of complicated MC twin pregnancies undergoing selective fetal reduction at a tertiary fetal center over a 20-year period. Obstetric and perinatal outcomes were compared. RESULTS: 105 procedures met inclusion criteria: 74 RFAs, 17 lasers and 14 BCs. Procedure duration was significantly shorter for RFA (27.4 ± 15.8 minutes) compared to BC (91.7 ± 38.7 minutes) and laser (83.4 ± 40.4 minutes), P < .0001). The incidence of preterm prelabor rupture of membranes (PPROM) and co-twin demise did not differ between groups, however preterm delivery <34 weeks occurred less frequently following RFA (29.7%), compared to laser (64.7%) or BC (42.9%) (P = .02); delivery <37 weeks was also less frequent following RFA (45.9%), compared to laser (76.5%) or BC (78.6%)(P = .01). The difference in preterm birth<34 weeks between RFA and laser was maintained after adjusting for cord occlusion indication and amnionicity (OR 3.96, 95% CI 1.27-12.31). CONCLUSIONS: In our experience, RFA procedures were simpler, faster and associated with a lower risk of preterm delivery <34 and <37 weeks, compared to laser or BC.

Changes in rate of preterm birth and adverse pregnancy outcomes attributed to preeclampsia after introduction of a refined definition of preeclampsia: A population-based study.

INTRODUCTION: Since 2013, various guidelines for hypertension in pregnancy have been refined, no longer requiring proteinuria as a requisite criterion for preeclampsia. We aimed to evaluate the impact of the new definition on preterm birth (PTB) and adverse pregnancy outcomes. MATERIAL AND METHODS: Women delivering in Ontario between April 2012 and November 2016 were included. Delivery <24+0/7 weeks, major fetal anomalies or preexisting renal disease were excluded. The primary outcome was livebirth <37, <34 or <32 weeks. Rates, adjusted rate ratios (aRR) and ratio of the rate ratio (RRR) were used to compare outcomes in the 2 years after the new Society of Obstetricians and Gynaecologists of Canada (SOGC) guideline (December 2014-November 2016; period 2) vs the 2 years before (April 2012-March 2014; period 1), among women with and without preeclampsia. RESULTS: In all, 268 543 and 267 964 births in periods 1 & 2, respectively, were included. Respective preeclampsia rates increased significantly from 3.9% to 4.4% (p < 0.001), with no change in maternal morbidity rates. In preeclamptic women, respective rates of PTB <37 weeks were 21.0% and 20.7% (aRR 1.01, 95% confidence interval [CI] 1.00-1.02), with significant aRR for PTB <34 (0.86, 95% CI 0.77-0.96) and <32 weeks (0.79, 95% CI 0.67-0.94). A similar aRR was observed in women without preeclampsia. In preeclamptic women, composite severe neonatal morbidity decreased after guideline change (aRR 0.95, 95% CI 0.91-0.99), a finding not observed in women without preeclampsia (RRR 0.95, 95% CI 0.91-0.99). CONCLUSIONS: The new definition of preeclampsia was associated with increased disease rates, a modest reduction in adverse neonatal outcomes and no change in maternal outcomes.

The Contribution of an Infectious Workup in Understanding Stillbirth.

OBJECTIVE: This study was aimed to assess the utility of diagnostic tests of maternal and fetal infection in the evaluation of stillbirth. STUDY DESIGN: A single-center retrospective study from January 2011 to December 2016 of all women presenting to the hospital with intrauterine fetal death at or after 20 weeks of gestation. Standard evaluation included review of medical records, clinical and laboratory inflammatory workup, maternal serologies, fetal autopsy, placental pathology, and fetal and placental cultures. A suspected infectious etiology was defined as meeting at least two diagnostic criteria, and only after exclusion of any other identifiable stillbirth cause. RESULTS: During the 7-year study period, 228 cases of stillbirth were diagnosed at our center. An infectious etiology was the suspected cause of stillbirth in 35 cases (15.3%). The mean gestational age of infection-related stillbirth was 28 1/7 (range: 22-37) weeks, while for a noninfectious etiology, it was 34 0/7 (range: 25-38) weeks (p = 0.005). Placental histological findings diagnostic of overt chorioamnionitis and funisitis were observed in 31 (88.5%) cases. In 16 (45.7%) cases the placental and fetal cultures were positive for the same pathogen. Serology of acute infection was positive in three (8.5%) of the cases. CONCLUSION: Maternal and fetal infectious workup is valuable in the investigation of stillbirth, particularly before 30 weeks of gestation and should be considered a part of standard evaluation.